The c.*52 A/G and c.*773 A/G Genetic Variants in the UTR′3 of the LDLR Gene Are Associated with the Risk of Acute Coronary Syndrome and Lower Plasma HDL-Cholesterol Concentration
Abstract
:1. Introduction
2. Materials and Methods
2.1. Characteristics of the Study Population
2.2. Laboratory Analyses
2.3. Genetic Analysis
2.4. Inheritance Models Analysis
2.5. Analysis of the Haplotypes
2.6. Functional Prediction Analysis
2.7. Statistical Analysis
3. Results
3.1. Characteristics of the Study Population
3.2. Allele and Genotype Frequencies
3.3. Linkage Disequilibrium Analysis
3.4. Functional Prediction
3.5. Association of Polymorphisms and Haplotypes with Plasma Lipids Levels
4. Discussion
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
LDLR | Low-density lipoprotein receptor |
UTR′3 | Untranslated region-′3 |
HDL-C | High-density lipoprotein-cholesterol |
LDL-C | Low-density lipoprotein-cholesterol |
T2DM | Type 2 diabetes mellitus |
SNP | Single nucleotide polymorphism |
ACS | Acute coronary syndrome |
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Characteristic | ACS Patients (n = 618) | Healthy Controls (n = 666) | p-Value | |
---|---|---|---|---|
Median (percentile 25–75) | Median (percentile 25–75) | |||
Age (years) | 58 (51–65) | 54 (49–59) | 0.001 | |
Gender n (%) | Male | 505 (82) | 453 (68) | <0.001 |
Female | 113 (18) | 213 (32) | ||
BMI (kg/m2) | 27 (25–29) | 28 (26–31) | 0.521 | |
Blood pressure (mmHg) | Systolic | 132 (114–144) | 117 (106–126) | <0.001 |
Diastolic | 80 (70–90) | 73 (67–78) | <0.001 | |
Glucose (mg/dL) | 159 (102–188) | 98 (84–99) | <0.001 | |
Total cholesterol (mg/dL) | 164(128–199) | 191 (165–210) | <0.001 | |
HDL-C (mg/dL) | 39 (34–45) | 44 (35–53) | 0.017 | |
LDL-C (mg/dL) | 106 (75–132) | 116 (94–134) | <0.001 | |
Triglycerides (mg/dL) | 169 (109–201) | 176 (113–208) | 0.301 | |
Hypertension n (%) | Yes | 350 (57) | 201 (30) | <0.001 |
Type II diabetes mellitus n (%) | Yes | 216 (35) | 63 (9) | <0.001 |
Dyslipidemia n (%) | Yes | 528 (85) | 479 (72) | <0.001 |
Smoking n (%) | Yes | 222 (36) | 147 (22) | <0.001 |
Polymorphic Site | n (Genotype Frequency) | Model | OR (95%CI) | pC | n (Allele Frequency) | OR | 95%CI | pC | |||
---|---|---|---|---|---|---|---|---|---|---|---|
LDLR UTR′3 | c.*52 A/G (rs14158) | *Risk allele | |||||||||
Control | GG | AG | AA | G | *A | A vs. G | |||||
(n = 666) | 385 (0.578) | 252 (0.378) | 29 (0.043) | Co-dominant | 2.02 (1.18–3.46) | 0.033 | 1022 (0.766) | 310 (0.232) | |||
Dominant | 1.13 (0.88–1.45) | 0.35 | 1.20 | 1.00–1.44 | 0.02 | ||||||
ACS | 337 (0.545) | 231 (0.374) | 50 (0.081) | Recessive | 2.00 (1.18–3.39) | 0.009 | 905 (0.732) | 331 (0.267) | |||
(n = 618) | Over-dominant | 0.96 (0.74–1.24) | 0.73 | ||||||||
Additive | 1.20 (0.98–1.45) | 0.075 | |||||||||
LDLR UTR′3 | c.*504 A/G (rs2738465) | ||||||||||
Control | GG | AG | AA | G | *A | A vs. G | |||||
(n = 666) | 323 (0.485) | 283 (0.425) | 60 (0.090) | Co-dominant | 1.50 (0.99–2.26) | 0.16 | 929 (0.696) | 403 (0.302) | |||
Dominant | 1.15 (0.90–1.47) | 0.27 | 1.18 | 1.00–1.40 | 0.02 | ||||||
ACS | 280 (0.453) | 256 (0.414) | 82 (0.133) | Recessive | 1.45 (0.98–2.16) | 0.06 | 816 (0.660) | 420 (0.339) | |||
(n = 618) | Over-dominant | 0.99 (0.77–1.27) | 0.94 | ||||||||
Additive | 1.17 (0.97–1.41) | 0.09 | |||||||||
LDLR UTR′3 | c.*773 A/G (rs2738466) | ||||||||||
Control | AA | AG | GG | A | *G | G vs. A | |||||
(n = 666) | 386 (0.580) | 250 (0.375) | 30 (0.045) | Co-dominant | 2.04 (1.35–3.45) | 0.027 | 1022 (0.766) | 310 (0.232) | |||
Dominant | 1.14 (0.88–1.46) | 0.32 | 1.22 | 1.02–1.146 | 0.01 | ||||||
ACS | 335 (0.542) | 231 (0.374) | 52 (0.084) | Recessive | 2.01 (1.20–3.38) | 0.007 | 901 (0.728) | 335 (0.271) | |||
(n = 618) | Over-dominant | 0.96 (0.74–1.24) | 0.73 | ||||||||
Additive | 1.21 (0.99–1.48) | 0.062 |
c.*52 A/G | c.*504 A/G | c.*773 A/G | ACS (n = 618) | Controls (n = 666) | OR | 95%CI | pC |
---|---|---|---|---|---|---|---|
Haplotype | Hf | Hf | |||||
G | G | A | 0.658 | 0.695 | 0.84 | 0.71–0.99 | 0.023 |
A | A | G | 0.267 | 0.230 | 1.22 | 1.02–1.46 | 0.016 |
A | G | A | 0.070 | 0.069 | 1.03 | 0.76–1.39 | 0.446 |
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Vargas-Alarcon, G.; Perez-Mendez, O.; Ramirez-Bello, J.; Posadas-Sanchez, R.; Gonzalez-Pacheco, H.; Escobedo, G.; Nieto-Lima, B.; Carreon-Torres, E.; Fragoso, J.M. The c.*52 A/G and c.*773 A/G Genetic Variants in the UTR′3 of the LDLR Gene Are Associated with the Risk of Acute Coronary Syndrome and Lower Plasma HDL-Cholesterol Concentration. Biomolecules 2020, 10, 1381. https://doi.org/10.3390/biom10101381
Vargas-Alarcon G, Perez-Mendez O, Ramirez-Bello J, Posadas-Sanchez R, Gonzalez-Pacheco H, Escobedo G, Nieto-Lima B, Carreon-Torres E, Fragoso JM. The c.*52 A/G and c.*773 A/G Genetic Variants in the UTR′3 of the LDLR Gene Are Associated with the Risk of Acute Coronary Syndrome and Lower Plasma HDL-Cholesterol Concentration. Biomolecules. 2020; 10(10):1381. https://doi.org/10.3390/biom10101381
Chicago/Turabian StyleVargas-Alarcon, Gilberto, Oscar Perez-Mendez, Julian Ramirez-Bello, Rosalinda Posadas-Sanchez, Hector Gonzalez-Pacheco, Galileo Escobedo, Betzabe Nieto-Lima, Elizabeth Carreon-Torres, and Jose Manuel Fragoso. 2020. "The c.*52 A/G and c.*773 A/G Genetic Variants in the UTR′3 of the LDLR Gene Are Associated with the Risk of Acute Coronary Syndrome and Lower Plasma HDL-Cholesterol Concentration" Biomolecules 10, no. 10: 1381. https://doi.org/10.3390/biom10101381